Implementation study of the 2021 German guideline for diagnosis and treatment of multiple sclerosis.

BACKGROUND: In May 2021, a new guideline on the diagnosis and treatment of multiple sclerosis and related disorders was released in Germany. Since the success of a guideline depends on how it integrates into everyday clinical practice, the German Society for Neurology (DGN) has launched a multimethod implementation project. Here we report on the results based on the consultation version of the guideline. METHODS: We used qualitative and quantitative data analyses to capture the nature and extent of barriers and facilitating factors to the implementation. We centered on the guideline's chapter A on diagnosis, relapse therapy, and immunotherapy of multiple sclerosis. We performed nine online focus group discussions and a web-based survey and analyzed emails and letters with comments from stakeholders and independent parties that were sent spontaneously or by invitation. RESULTS: 94 neurologists answered the survey, and ≥70% agreed with the recommendations of the guideline on each major content topic. Barriers to implementation were detected in group discussions and written input. The most controversial issues of the guideline were "early treatment", "criteria for starting or switching therapy", "stepwise escalation versus early aggressive treatment", "classification of drugs into three categories of efficacy" and the scenarios on "treatment cessation". Some appreciated the highly structured recommendations, but others felt that the guideline restricts the free choice of therapy, or they were afraid of recourse claims. Some considered the guideline as too cautious regarding treatment initiation, possibly delaying necessary therapies. Others appreciated that conflicts of interests of the guideline's authoring group were minimized and thought that the new guideline is clearer, more extensive and practical. CONCLUSION: In contrast to the survey, feedback in the focus group discussions and from individuals was diverse and sometimes more critical. Based on the overall feedback rate of about 250 people in relation to the number of 6500 board-certified neurologists in Germany, the overall appreciation of the guideline can only be considered as an indicator and not proof of acceptance. Results of this analysis were incorporated into several adjustments to the final guideline of 2021. Since the guideline is to be updated regularly under the auspices of a "living guideline", active interaction with users will continue to matter and help to improve it.

Multiband spectroscopy of ultracold fermions: observation of reduced tunneling in attractive Bose-Fermi mixtures.

We perform a detailed experimental study of the band excitations and tunneling properties of ultracold fermions in optical lattices. Employing a novel multiband spectroscopy for fermionic atoms, we can measure the full band structure and tunneling energy with high accuracy. In an attractive Bose-Fermi mixture we observe a significant reduction of the fermionic tunneling energy, which depends on the relative atom numbers. We attribute this to an interaction-induced increase of the lattice depth due to the self-trapping of the atoms.

[Assessment of benefit and efficiency of innovative medical devices]. / Nutzen- und Wirtschaftlichkeitsbewertung der biomedizinischen Technik.

Medical devices cover a wide spectrum of products with very different diagnostic and therapeutic applications. However, for market licensing, uniform rules apply. Uniform rules are also valid for coverage decisions in German health care. In this article, the criteria for the assessment of benefit and efficiency of innovative biomedical technologies are described from the perspective of the statutory health insurance system. The key concepts relevant in the mandatory health insurance' "innovation"' "benefit", and "economic efficiency" are characterized. Only measurable effects of an intervention which lead to a more than marginal improvement in prognosis, symptoms, or quality of life as compared to a standard treatment are considered as beneficial. An innovative device is, therefore, subject to a benefit assessment if it is not yet reimbursed (or not yet part of the benefit package), when it is relevant to the health care system and a high public interest exists. In addition, it is important to consider a positive benefit assessment as a part of the value added chain to avoid conflicts of interest. Within the scope of early technology assessment, some conclusions can already be drawn in the early developmental stage of a device.

Does Visual Impairment Affect Social Ties in Late Life? Findings of a Multicenter Prospective Cohort Study in Germany.

OBJECTIVE: To investigate how visual impairment affects social ties in late life longitudinally. DESIGN: Population-based prospective cohort study. SETTING: Individuals in old age were recruited via general practitioners' offices (at six study centers) in Germany. They were interviewed every 18 months. PARTICIPANTS: Individuals aged 75 years and above at baseline. Follow-up wave 2 (36 months after baseline, n=2,443) and wave 4 (72 months after baseline, n=1,618) were used for the analyses presented here. MEASUREMENTS: Social ties were assessed using the 14-item form of the questionnaire for social support (F-SozU K-14). Visual impairment was self-rated on a three level Likert scale (no impairment, mild visual impairment, or severe/profound visual impairment). RESULTS: Adjusting for sociodemographic factors, hearing impairment and comorbidity, fixed effects regressions revealed that the onset of mild visual impairment decreased the social support score, in particular the emotional support score. Additionally, the onset of mild hearing impairment decreased the social support score in men. Moreover, increasing age decreased the social support score in the total sample and in both sexes. Loss of spouse and increasing comorbidity did not affect the social support score. CONCLUSION: Our results highlight the importance of visual impairment for social ties in late life. Consequently, appropriate strategies in order to delay visual impairment might help to maintain social ties in old age.

Experimental reconstruction of the Berry curvature in a Floquet Bloch band.

Topological properties lie at the heart of many fascinating phenomena in solid-state systems such as quantum Hall systems or Chern insulators. The topology of the bands can be captured by the distribution of Berry curvature, which describes the geometry of the eigenstates across the Brillouin zone. Using fermionic ultracold atoms in a hexagonal optical lattice, we engineered the Berry curvature of the Bloch bands using resonant driving and show a full momentum-resolved measurement of the ensuing Berry curvature. Our results pave the way to explore intriguing phases of matter with interactions in topological band structures.

[Use of bone densitometry in the framework of prevention and therapy of osteoporosis. Example of a systematic evaluation (health technology assessment)]. / Stellenwert der Osteodensitometrie im Rahmen von Prävention und Therapie der Osteoporose. Beispiel einer systematischen Verfahrensbewertung in der Medizin (Health Technology Assessment).

There is an ongoing controversy concerning the use of bone density measurements within therapeutic and preventive strategies of osteoporosis. Since there are no randomized controlled trials evaluating the effectiveness of bone density measurement with subsequent therapy we used a "critical pathway" model to determine possible benefit of tertiary, secondary and primary preventive strategies utilizing bone density measurement. In a first step data for fracture risk in each group are extracted from the literature. The second step outlines possible benefit from therapeutic studies. It may be estimated that in groups of patients with prevalent fractures use of bone density measurement and therapy according to bone density values may reduce fracture rates up to 30%. Bone density measurements performed with secondary preventive intent, however will probably lead to a reduction of fracture rates markedly below 10%. A set of risk factors that allows identification of a high risk group that may benefit from bone density measurement and subsequent therapy to a relevant extent remains to be developed. Primary preventive strategies do not require bone density measurements.

[International practice guidelines on the management of osteoporosis-- assessment of methodologic quality]. / Internationale Praxisleitlinien zum Thema Osteoporose--Bewertung der methodischen Qualität.

To a growing extent evidence-based clinical practice guidelines are considered helpful in supporting high quality medical care. Our study assessed the methodological quality of 20 clinical practice guidelines on the management of osteoporosis. Results indicated that only 2 out of 20 guidelines were developed with sufficient methodological rigour to be called evidence-based--none of them from Germany. Comparative reports including quality assessments may not only be helpful for clinicians to choose an appropriate guideline for their daily practice but also to stimulate guideline developers to use more rigorous methodology.

[Effectiveness of back-school programs in controlled trials. A review of the literature]. / Die Wirksamkeit von Rückenschulprogrammen in kontrollierten Studien. Eine Literaturübersicht.

Backschools are utilized for primary, secondary and tertiary prevention of nonspecific low back pain while there is considerable doubt concerning their effectiveness. We present the results of controlled clinical trials that examine the effectiveness of back schools as reported in recent systematic reviews of the literature. An extensive literature search for systematic reviews summarizing the results of controlled trials was performed. Publications which satisfied a number of inclusion criteria concerning methodology and content were critically appraised. Their main results and conclusions are presented and discussed.

[Rapid reviews for evidence-based decision support. (Restricting) requirements]. / Entscheidungsunterstützung durch Kurzstellungnahmen zur Evidenzlage. (Verzicht auf) Anforderungen.

Since evidence-based decision making is increasingly gaining acceptance among German health care authorities the need for evidence-based support for time-critical decisions becomes obvious. The best method to identify and summarize the available evidence is the conduct of systematic reviews of the literature. However, generally systematic reviews are not applicable in matters of urgency, because of their time consuming preparation. Concepts for "rapid reviews" are urgently required which ensure that these reviews still produce reliable results. The article proposes strategies to accelerate the preparation of a systematic review and discusses their possible influences on the conclusions of the review. Research efforts are needed to clarify which of the accelerations actually yield valid results.

[Health technology assessment in the international context: where does Germany stand? For the "German Scientific Working Group Technology Assessment for Health care"]. / Health Technology Assessment im internationalen Kontext: Wo steht Deutschland? Für die "German Scientific Working Group Technology Assessment for Health Care".

The evaluation of medical technologies, Health Technology Assessment (HTA), is gaining more and more importance in Germany. Starting from a comprehensive definition of the term medical technology, this article first describes the development of HTA since the seventies as an instrument for improving decision-making in health policy. HTA is presented as a repetitive cycle of a sequence of steps starting with the prioritization of topics to be evaluated to the analysis of the impact of the results. Current trends in the further improvement of HTA methods are described, such as the formalization of the topic selection. The current situation in Germany is presented with regard to the regulation of licensing/market entry, coverage by the statutory health insurance, and the utilization of medical technologies. Finally, current activities in the field of HTA in Germany as well as the role of the German Scientific Working Group Technology Assessment for Health Care are discussed.

Designing trials for pressure ulcer risk assessment research: methodological challenges.

For decades various pressure ulcer risk assessment scales (PURAS) have been developed and implemented into nursing practice despite uncertainty whether use of these tools helps to prevent pressure ulcers. According to current methodological standards, randomised controlled trials (RCTs) are required to conclusively determine the clinical efficacy and safety of this risk assessment strategy. In these trials, PURAS-aided risk assessment has to be compared to nurses' clinical judgment alone in terms of its impact on pressure ulcer incidence and adverse outcomes. However, RCTs evaluating diagnostic procedures are prone to specific risks of bias and threats to the statistical power which may challenge their validity and feasibility. This discussion paper critically reflects on the rigour and feasibility of experimental research needed to substantiate the clinical efficacy of PURAS-aided risk assessment. Based on reflections of the methodological literature, a critical appraisal of available trials on this subject and an analysis of a protocol developed for a methodologically robust cluster-RCT, this paper arrives at the following conclusions: First, available trials do not provide reliable estimates of the impact of PURAS-aided risk assessment on pressure ulcer incidence compared to nurses' clinical judgement alone due to serious risks of bias and insufficient sample size. Second, it seems infeasible to assess this impact by means of rigorous experimental studies since sample size would become extremely high if likely threats to validity and power are properly taken into account. Third, means of evidence linkages seem to currently be the most promising approaches for evaluating the clinical efficacy and safety of PURAS-aided risk assessment. With this kind of secondary research, the downstream effect of use of PURAS on pressure ulcer incidence could be modelled by combining best available evidence for single parts of this pathway. However, to yield reliable modelling results, more robust experimental research evaluating specific parts of the pressure ulcer risk assessment-prevention pathway is needed.

Role of interactions in 87Rb-40K Bose-Fermi mixtures in a 3D optical lattice.

We investigate the effect of interspecies interaction on a degenerate mixture of bosonic 87Rb and fermionic 40K atoms in a three-dimensional optical lattice potential. Using a Feshbach resonance, the 87Rb-40K interaction is tuned over a wide range. Through an analysis of the 87Rb momentum distribution, we find a pronounced asymmetry between strong repulsion and strong attraction. In the latter case, we observe a marked shift in the superfluid to Mott insulator transition, which we attribute to a renormalization of the Bose-Hubbard parameters due to self-trapping.

[The German Network for Evidence-based Medicine -- DNEbM]. / Das Deutsche Netzwerk Evidenzbasierte Medizin -- DNEbM.

The German Network for Evidence-based Medicine (DNEbM) was founded in October 2000. A major impetus for the development of evidence-based medicine (EBM) in Germany came in the mid-1990s from the German Cochrane Initiative, which referred to the principles and activities of the international Cochrane Collaboration. The Network's primary mission is to establish a competence and reference centre for all aspects of evidence-based medicine. Central to this mission is to encourage projects that are concerned with scientific and methodological problems, aspects of professional development and the question of how to translate EBM into clinical practice. With currently more than 600 individual members the DNEbM is the most important society concerned with EBM in the German-speaking region in Europe. Until now, the DNEbM has initiated the development of curricula for EBM and health technology assessment (HTA) for undergraduate and continuing medical education. In addition, position papers regarding hot topics such as prostate cancer screening with PSA or registration of randomised controlled trials were published. The Network's HTA section comprises experts from universities, institutes, health care administration and industry. Currently, the HTA section is developing an Internet-based course for users and doers of HTA reports in Germany.

Low prevalence of diphtheria antitoxin in children and adults in northern Germany.

Recent outbreaks of diphtheria in neighbouring eastern European countries and in the Russian Federation prompted us to evaluate immunity to diphtheria in a sample of 400 healthy individuals (210 male, 190 female) from northern Germany. An age-stratified study population was chosen, including newborns, children, adults and elderly persons over 60 years divided into 8 subgroups of 50 persons each. Diphtheria antitoxin was tested by enzyme immunoassay. The median antitoxin titre was 0.39 IU/ml. There was no difference in the median antitoxin titres of men and women. Inadequate immunity to diphtheria was detected in more than 90% of the 400 individuals tested, including 4% who completely lacked immunity (titre < 0.01 IU/ml), a further 20% with minimal protection (titre 0.01-0.1 IU/ml) and the majority of 69% who showed relative protection for less than one year (titre 0.1-1.0 IU/ml). Only 7% exhibited lasting protection for more than five years (titre > 1.1). Newborns and persons over 50 years of age constituted the least protected groups, with significantly lower median antitoxoid titres than the other age groups (p < 0.001). The absence of protective immunity in 7 of the 50 newborns examined (14%) reflects the inadequate protection of women of reproductive age. Children aged 1 to 10 years were the best immunized and protected group. The results suggest that routine booster immunizations of the majority of the adult population would be advisable in view of the ongoing migration from and the visits to high-risk areas.

[Rapid assessments"--quick evaluation of medical technology]. / "Rapid Assessments"--schnelle Bewertung medizinischer Technologien.

Assessing the clinical, economical and other consequences of medical technologies (health technology assessment, HTA) is an important instrument to support decisions in many health care systems. A comprehensive HTA, however, is time-consuming and costly while, on the other hand, decisions have to be made quickly. A number of international HTA programmes established rapid assessment tracks although they are variable in scope and methods. In the first part of this paper, these programmes were compared with respect to scope, methods and time to complete assessments. It can be shown from this comparison that there is no common definition of "rapid assessments". In the second part of the paper, a model for processing rapid assessment in the German context is introduced and discussed. The model aims at rapid assessments serving the needs of German decision-makers and ensuring high scientific quality at the same time. The model consists of a modular system that is tailored to the actual demand of the decision-maker. Modules are obligatory (such as a systematic literature search) or optional (such as meta-analysis). All modules are subject to standardisation as far as possible. However, it should be kept in mind that a close collaboration between commissioners and executives of an HTA is necessary to focus on the question and work out the HTA accordingly.